| IED ID | IndEnz0018000715 |
| Enzyme Type ID | peroxidase000715 |
| Protein Name |
Thyroid peroxidase TPO EC 1.11.1.8 |
| Gene Name | Tpo |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MRTLGAMAVMLVVMGTAIFLPFLLRSRDILGGKTMTSHVISVVETSQLLVDNAVYNTMKRNLKKRGVLSPAQLLSFSKLPESTSGAISRAAEIMETSIQVMKREQSQFSTDALSADILATIANLSGCLPFMLPPRCPDTCLANKYRPITGVCNNRDHPRWGASNTALARWLPPVYEDGFSQPRGWNPNFLYHGFPLPPVREVTRHLIQVSNEAVTEDDQYSDFLPVWGQYIDHDIALTPQSTSTAAFWGGVDCQLTCENQNPCFPIQLPSNSSRTTACLPFYRSSAACGTGDQGALFGNLSAANPRQQMNGLTSFLDASTVYGSSPGVEKQLRNWSSSAGLLRVNTLHLDSGRAYLPFASAACAPEPGAPHANRTPCFLAGDGRASEVPALAAVHTLWLREHNRLATAFKAINTHWSANTAYQEARKVVGALHQIITMRDYIPKILGPDAFRQYVGPYEGYNPTVNPTVSNVFSTAAFRFGHATVHPLVRRLNTDFQDHTELPRLQLHDVFFRPWRLIQEGGLDPIVRGLLARPAKLQVQEQLMNEELTERLFVLSNVGTLDLASLNLQRGRDHGLPGYNEWREFCGLSRLDTGAELNKAIANRSMVNKIMELYKHADNIDVWLGGLAEKFLPGARTGPLFACIIGKQMKALRDGDRFWWENSHVFTDAQRQELEKHSLPRVICDNTGLTRVPVDAFRIGKFPQDFESCEEIPSMDLRLWRETFPQDDKCVFPEKVDNGNFVHCEESGKLVLVYSCFHGYKLQGQEQVTCTQNGWDSEPPVCKDVNECADLTHPPCHSSAKCKNTKGSFQCVCTDPYMLGEDEKTCIDSGRLPRASWVSIALGALLIGGLASLSWTVICRWTHADKKSTLLITERVTMESGFRKSQESGISPQKAEVQDAEQEPAYGSRVLLCE |
| Enzyme Length | 914 |
| Uniprot Accession Number | P14650 |
| Absorption | |
| Active Site | ACT_SITE 233; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298 |
| Activity Regulation | |
| Binding Site | BINDING 232; /note="Heme b; covalent, via 2 links"; /evidence="ECO:0000250"; BINDING 387; /note="Heme b; covalent, via 2 links"; /evidence="ECO:0000250" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=2 H(+) + H2O2 + 2 iodide = diiodine + 2 H2O; Xref=Rhea:RHEA:23336, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:17606; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; CATALYTIC ACTIVITY: Reaction=[thyroglobulin]-L-tyrosine + H(+) + H2O2 + iodide = [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48956, Rhea:RHEA-COMP:12274, Rhea:RHEA-COMP:12275, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:46858, ChEBI:CHEBI:90870; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; CATALYTIC ACTIVITY: Reaction=[thyroglobulin]-3-iodo-L-tyrosine + H(+) + H2O2 + iodide = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48960, Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:90870, ChEBI:CHEBI:90871; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; CATALYTIC ACTIVITY: Reaction=2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-dehydroalanine + [thyroglobulin]-L-thyroxine + 2 H2O; Xref=Rhea:RHEA:48964, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12277, Rhea:RHEA-COMP:12278, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:90871, ChEBI:CHEBI:90872, ChEBI:CHEBI:90873; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; CATALYTIC ACTIVITY: Reaction=[thyroglobulin]-3,5-diiodo-L-tyrosine + [thyroglobulin]-3-iodo-L-tyrosine + H2O2 = [thyroglobulin]-3,3',5-triiodo-L-thyronine + [thyroglobulin]-dehydroalanine + 2 H2O; Xref=Rhea:RHEA:48968, Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12278, Rhea:RHEA-COMP:12279, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:90870, ChEBI:CHEBI:90871, ChEBI:CHEBI:90873, ChEBI:CHEBI:90874; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; |
| DNA Binding | |
| EC Number | 1.11.1.8 |
| Enzyme Function | FUNCTION: Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4). {ECO:0000250|UniProtKB:P09933}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis. |
| nucleotide Binding | |
| Features | Active site (1); Binding site (2); Chain (1); Disulfide bond (10); Domain (2); Glycosylation (5); Metal binding (6); Region (1); Sequence conflict (4); Signal peptide (1); Site (1); Topological domain (2); Transmembrane (1) |
| Keywords | Calcium;Disulfide bond;EGF-like domain;Glycoprotein;Heme;Hydrogen peroxide;Iron;Membrane;Metal-binding;Oxidoreductase;Peroxidase;Reference proteome;Signal;Sushi;Thyroid hormones biosynthesis;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. |
| Modified Residue | |
| Post Translational Modification | PTM: Heme is covalently bound through a H(2)O(2)-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface (By similarity). {ECO:0000250}.; PTM: Cleaved in its N-terminal part. {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..31; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12748414; 15917231; 17379648; 17709379; 17714035; 20629314; 21619833; 23064013; 24625548; 26610751; 31439949; |
| Motif | |
| Gene Encoded By | |
| Mass | 101,460 |
| Kinetics | |
| Metal Binding | METAL 234; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 313; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 315; /note=Calcium; via carbonyl oxygen; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 317; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 319; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 482; /note=Iron (heme b axial ligand); /evidence=ECO:0000255|PROSITE-ProRule:PRU00298 |
| Rhea ID | RHEA:23336; RHEA:48956; RHEA:48960; RHEA:48964; RHEA:48968 |
| Cross Reference Brenda |